Some of ingredients contained in various citrus fruits are known to have a variety of bioactivities. Auraptene, a kind of coumarin compounds, is known to have bioactivity such as antitumor activity, antioxidative activity, anti-inflammatory action, PPAR agonist activity, antibacterial activity, antiplatelet activity and antileishmanial activity and there have been proposed an ameliorating agent for metabolic syndrome using the effect of auraptene (Patent Literatures 1: Domestic Re-publication of PCT International Application No. 07-132893 and 2: Domestic Re-publication of PCT International Application No. 06-077972), a drug for preventing or treating neurotransmission disorder (Patent Literature 3: Japanese PCT National Publication No. 2008-517879), an inhibitor of Epstein-Barr virus early antigen induction (Patent Literature 4: Japanese Patent Application Laid-Open (JP-A) No. 09-157166) and the like.
In addition, as an ingredient of citrus fruits having an effect of promoting osteoblast differentiation, hesperetin (Non-Patent Literatures 1 and 2), naringin (Non-Patent Literature 3) and β-cryptoxanthin (Non-Patent Literature 4) are reported. Coumarin compounds are described in Non-Patent Literatures 5 to 9.
JP-A No. 2006-083151 (Patent Literature 5) describes a composition for preventing and improving osteoporosis characterized by containing an extract of Citrus unshiu fruit and pericarp, which is based on the bone resorption inhibition effect due to inhibition of osteoclast differentiation by β-cryptoxanthin and hesperidin.
JP-A No. 2006-008625 (Patent Literature 6) describes a bone metabolism improving agent including summer orange (Hyuga natsu; C. tamurana) treatment product. As the effects on osteoblasts, the growth stimulating effect and IL-6 production promoting effect are described. However, the differentiation promoting effect is not described.
Thus, literatures reporting the osteoblast differentiation promoting effect or bone formation promoting effect of auraptene and an analog thereof cannot be found.